Mild TBI (mTBI) has traditionally been defined by a Glasgow Coma Scale (GCS) score of 13–15, loss of consciousness (LOC) less than 30 min, and posttraumatic amnesia (PTA) less than 24 h [3]. Brief LOC may also be associated with mTBI; however, its usefulness in predicting symptoms subsequent to mTBI is questionable. Research has shown that LOC is not associated with total number of symptoms or duration of symptoms among athletes who sustained concussions [4]. Some persons report experiencing symptoms consistent with post-concussion syndrome (PCS), which can be grouped into three clusters: somatic, affective, and cognitive [5]. Somatic symptoms typically include headache, fatigue, and dizziness. The affective cluster often includes irritability, anxiety, depressed mood, and sleep difficulties. The most commonly reported cognitive changes include slowed processing speed, poor attention, and difficulty with short-term memory [5–7].

It is noteworthy, however, that PCS symptoms are not specific to mTBI [8, 9] and some individuals have questioned the construct validity of this diagnosis, including the authors of the Diagnostic and Statistical Manual of Mental Disorders—IV-Text Revision [10]. mTBI is listed as a diagnosis under the category of Criteria Sets and Axes Provided for Further Study, due to the limited empirical evidence for this disorder as a distinct entity. Furthermore, in prospective studies, the presence of mTBI did not predict PCS symptoms at 5 days post-injury, rather the presence of a depressive or anxiety disorder and female gender were most strongly related to PCS symptom reporting [6, 8, 11]. Rates of PCS symptoms have been found to be roughly equivalent among mTBI patients and trauma controls, which indicates that mTBI is not specifically predictive of PCS [12]. Other studies have found similar rates of PCS symptoms among normal controls and outpatients [13, 14]. Furthermore, PCS symptoms have not been found to be related to objectively measured cognitive functioning [12]. Rather subjective complaints of deteriorating cognitive functioning are likely related to non-brain injury factors [15, 16]. For studies that have noted PCS symptoms, symptoms resolved within 16 days of injury [4] and poor medical health, mental health, and marital status at baseline (being widowed, divorced, or separated) were more predictive of complaints such as fatigue at 12 months than was injury [17]. Persons with history of mTBI may attribute fatigue, as well as other PCS symptoms, to their injuries but the symptoms may actually be associated with premorbid factors, psychological status, or other health-related factors. Thus, PCS symptoms appear to reflect psychological distress related to the events of the injury, pre-injury psychological distress, or non-clinical factors and are likely unrelated to the actual head injury especially when they occur after the first month.

Mild cognitive deficits may occur within the first few days after mTBI, often including difficulty with recall, slowed processing speed, and reduced attention. These symptoms may be due to the actual brain injury, but other causes such as injury-related pain and psychological distress cannot be ruled out [8]. Research has suggested that athletes sustaining concussions demonstrate full recovery on cognitive measures within 7–10 days (e.g., return to personal baseline) [18, 19]. In community samples of persons with mTBI deficits in verbal learning and attention as compared to controls were evident up to 1–6 months post-injury in some individuals, but many individuals did not show any cognitive impairment during this time period [20, 21]. Although subtle neuropsychological changes may be evident following mTBI, research has shown that these changes are often resolved within 3 months [8, 19].

Regarding functional outcomes, assessed with the GOS, research has shown that persons who have sustained mTBI have good outcomes in both the short and long terms [8]. Poor outcomes and lingering PCS symptoms appear to be unrelated to brain injury and likely related to psychological variables or litigation. For example, subjective cognitive and somatic complaints may be related to depression or anxiety [8, 22]. The literature also indicates a tendency for persons sustaining injuries to recall themselves as being healthier and happier prior to the injury. For example, persons who had sustained concussions 6 months previously underestimated their pre-concussion symptoms by 97 % [23]. This tendency has been referred to as the “good old days” bias, such that people overestimate the actual degree of change that has occurred since injury by underestimating premorbid symptoms [24–26]. Iverson et al. [25] found that pre-injury ratings of persons with mTBI were higher than ratings of control participants. As PCS symptoms are nonspecific, a person may associate negative events and feelings to an injury rather than normal emotional fluctuations, events, etc. The effects of litigation on recovery from mTBI are discussed later in this chapter in the mitigating factors section. Thus, consistent findings indicate full recovery following an uncomplicated mTBI in the vast majority of injured persons.

Research has also focused on the cumulative effects of sustaining repeated mTBIs, especially among athletes. Whereas some correlational studies have suggested a dose–response relationship between number of injuries and poorer neuropsychological status, a meta-analysis on multiple mTBIs by Belanger et al. [27] indicated that the literature revealed no overall significant effect on neurocognitive functioning or symptom complaints. Their results showed that sustaining multiple mTBIs has been associated with cognitive deficits in executive functioning and memory, but the effect size was small and the clinical significance was unclear. The authors concluded that sustaining two or more mTBIs has little relationship with cognitive performance several months later.

Some researchers have speculated that repeated trauma to the brain may accelerate degenerative processes later in life, such as mild cognitive impairment, Parkinson’s, Alzheimer’s, or some other type of neurodegenerative disease [28]. Findings concerning whether the length of recovery following subsequent mTBIs is longer than the first mTBI have been inconclusive [27, 28]. Among professional boxers, a review of the literature by Loosemore et al. [29] revealed that 10–20 % develop measurable long-term brain injury as indicated by clinical, radiologic, or histopathologic examination, but they found that amateur boxing was not associated with neurocognitive deterioration. A recent study on diffuse axonal injury (DAI) as measured by MRI showed no significant differences in frequencies of microhemorrhages between amateur boxers and controls [30]. A possible explanation for this discrepancy is that a head guard is not permitted in professional boxing, but is required in amateur boxing. Although the concepts of dementia pugilistica and chronic traumatic encephalopathy have been discussed in the media, there are very few well-controlled studies published in the neurology literature on these conditions and the studies have not controlled for other factors that could contribute to cognitive impairment such as premorbid learning disabilities, ADHD, and substance abuse.

The risk of “second-impact syndrome” has been identified, especially among athletes. This syndrome may occur when someone sustains a second concussion prior to complete healing from a previous concussion, usually within a few days to a week, which has been thought to lead to acute brain swelling and the possibility of fatality [19], but the probability of such an injury occurring is extremely low. Randolph and Kirkwood’s [31] review of the risks of sport-related concussion included an examination of the Catastrophic Sports Injury Database for 10 years of American football at all levels. These authors found that there was only one case of diffuse cerebral swelling at all levels of play over this time period, even though it was estimated that 40 % of players were returned to play when symptomatic [32]. Given the overall high rate of concussion, one would expect that if second impact syndrome was a common medical event, one would see more than one case in a 10-year span in this database. Additionally, given the return to play guidelines currently in place in the sports community, individuals are at a lower risk for this kind of event given that it already has a very low base rate. Research has indicated that when diffuse cerebral swelling is seen, it is most often in children and adolescents and represents a calcium subchannel mutation that is related to familial hemiplegic migraine [33, 34].

Complicated mTBI is a classification of TBI for cases in which GCS scores were between 13 and 15 with evidence of an intracranial bleed or lesion [35, 36]. Research has shown that a subgroup of persons with GCS scores in this range accompanied by intracranial bleeds had poorer outcomes, including neuropsychological status, than those who had sustained an uncomplicated injury [35]. Similarly, persons with GCS of 15 after TBI who required surgery after developing intracranial hematoma were also at risk for worse outcomes, such that only 65 % had a good outcome [37]. Research has shown an increased level of disability among persons with complicated mTBI at 6 months and 1 year as compared to those sustaining uncomplicated injuries [35, 36, 38, 39]. Persons sustaining complicated mTBIs have also been found to have significantly worse cognitive performances than control participants at 1 month post-injury, whereas those with uncomplicated mTBI had performances comparable to controls [40]. Furthermore, based on group data, persons sustaining complicated mTBIs have not been found to experience complete recovery of cognitive function to unimpaired levels by 1 year post-injury, which contrasts the 3 month recovery of neuropsychological status that is typical with mTBI [36].

Outcomes at 1 year post-injury among persons with complicated mTBI are actually more consistent with the outcomes following moderate TBI [36]. Functional outcomes were equivalent for those with complicated mTBI and moderate TBI, including the following domains: physical (FIM motor domain scores), cognitive (FIM cognitive domain), independence, employability (e.g., Disability Rating Scale), and community integration (Community Integration Questionnaire (CIQ)). The most common areas of cognitive impairment were processing speed, learning and memory, and word generation [35, 36].

Kashluba et al. [36] highlighted the importance of these findings in understanding the limitations of exclusively relying on GCS scores in the classification of TBI severity, as many of these individuals have length of unconsciousness or length of posttraumatic confusion (PTC) that are more consistent with moderate injuries. Persons with similar GCS scores in the mild range can have strikingly different outcomes if the injury was further complicated by an intracranial bleed. The authors argue for greater consideration of additional factors beyond GCS to predict outcome and determine severity of injury, including LOC, length of PTA, and time to follow commands. As the complicated mTBI group has been found to have similar outcomes to those sustaining moderate TBIs, more information regarding their outcomes is presented in the moderate-severe section of this chapter.

Moderate to severe TBI has typically been defined as a LOC longer than 30 min, PTA longer than 24 h, or a GCS of 9–12 for moderate severity and 3–8 for severe severity [3]. Following injury, persons with severe TBI may proceed through a series of stages, including coma, vegetative state, minimally conscious state, confused state (PTA), and recovery. While all will, by definition, have some period of coma (typically described as a GCS of 8 or below), most will never be in a vegetative state and it is unknown how many will be in a minimally conscious state at some point during recovery. For patients who are in vegetative and/or minimally conscious states, the duration of these states varies greatly [41]. Many people with moderate TBI, however, may never have been in a coma and none are in coma at hospital admission. Vegetative and minimally conscious states are not seen in moderate TBI unless there is deterioration due to some late occurring complication such as intracranial bleeding. However the confused state is seen in all patients with moderate or severe TBI. Incidence of persistent vegetative state (complete unawareness of self and environment lasting longer than 30 days with some preserved brainstem functioning such as eye opening) at 1 year post-injury is rare (e.g., 1 %; [41]). During a minimally conscious state, a person demonstrates inconsistent awareness of the environment and is inconsistent in following commands. The minimally conscious state is typically a temporary phase of recovery [42]. Subsequently, persons with TBI become responsive but confused. They often experience retrograde amnesia, such that they cannot recall events for a period of time prior to the head injury. In severe injuries, the last memory that can be recalled may have occurred days, months, or even longer before the injury. As recovery proceeds, the extent of retrograde amnesia typically shortens but the events surrounding the injury are not typically fully recalled. PTA is memory loss for events following the injury, including time in coma [43]. As other neurobehavioral impairments (e.g., disrupted sleep-wake cycle, disturbed consciousness, altered psychomotor activity, agitation) often accompany the memory and cognitive impairments seen in PTA, the broader term PTC is now often used to describe the early period of recovery following TBI [44]. PTC may be brief, such as several days, or long-lasting, such as longer than several weeks. PTA/PTC is typically considered to be resolved when a person demonstrates orientation and the ability to create and retain new memories [42]. PTA duration is best determined by serial administration of an orientation measure such as the Orientation Log or the Galveston Orientation and Amnesia Test. Agitated or restless behaviors during PTC have been associated with better outcomes than initial sluggishness or immobility [45]. Sherer et al. [46] found that patients who were more severely confused had worse outcomes in employability and productivity.

Neurobehavioral symptoms are common among those with moderate to severe TBI and typically include problems with irritability, temper, dizziness, sensitivity to noise, and blurred vision. Additionally, they may experience apathy or lack of initiative, as well as extreme fatigue or tiring easily [43]. The most common cognitive deficits following moderate to severe TBI include impairments in attention, processing speed, and learning and memory. Attentional difficulties can include distractibility, poor concentration, and reduced divided attention. Information processing speed is reduced, which can affect numerous other cognitive domains. Complex attention and executive functioning have frequently been found to be impaired following moderate to severe TBI [47, 48]. Some have argued that these deficits are the consequence of deficits in processing speed and attention [49]. Executive dysfunction may present as poor self-awareness, insight, or self-control, as well as impairments in organization, planning, and judgment. Memory problems typically consist of difficulties with learning new information, retaining it, and subsequently retrieving it. These difficulties may also be due to impairments in attention and executive functioning. Deficits in language and visuospatial constructional skills may also be present in more severe injuries [1]. Classic aphasia is relatively rare following TBI, unless there is a focal lesion [50]. Communication problems may be present due to word finding problems, organization, and executive functioning (e.g., social judgment, impulsivity). At 1 month post-injury, persons with moderate or severe TBI performed significantly worse on all cognitive measures than did controls, and those with severe injuries continued to perform worse than controls at 1 year post-injury [51].

Significant, long-term deficits are consistently found among persons with moderate to severe TBI. Moderate TBI appears to be associated with cognitive deficits for 6 months or longer post-injury; it is noteworthy that in a meta-analysis on cognitive outcome, Dikmen et al. [1] indicated that due to inconsistent use of cut points in severity labels, findings had to be tempered accordingly. Consistent with the dose–response theory, severe TBI is often associated with more extensive cognitive deficits than moderate TBI. For example, Novack et al. [52] found that the severely injured group had worse cognitive outcomes than did the moderately injured group at 12 months post-injury, and both groups were below normative cognitive performance levels.

Research on the timeline of cognitive recovery from moderate to severe TBI has generally indicated that the most rapid recovery occurs during the first 5 months post-injury [53]. Recovery typically continues between 6 months to 2 years post-injury [54] with the steepest rates of improvement between 2 and 5 months [53]. Millis et al. [55] found that further improvement can still be evident at 5 years post-injury. Rate and extent of recovery varies across cognitive domains, such that there is slower improvement for more complex functioning [56]. Consistent with this, Millis et al. [55] found that a greater proportion of persons with TBI demonstrated improvement on simpler memory tasks than on complex memory tasks. Recovery of reasoning and problem-solving skills was also variable, such that some people demonstrate sparing or improvement and others exhibit marked impairment up to several years post-injury. Their results also showed that the greatest improvements during years 1–5 post-injury occurred on measures of visuoconstruction (Block Design), problem-solving (Wisconsin Card Sorting Test), and complex attention (Trails B). Motor and visuospatial domains continue to show steep improvement throughout the first year post-injury [53]. Millis et al. [55] reported that tasks that require complex constructional skills and speed may be the most sensitive to late recovery (e.g., 1–5 years post-injury).

Residual cognitive deficits are common 2 years post-injury [54] and differences between persons with TBI and controls in attention, processing speed, memory, and executive functioning have been found up to 10 years post-injury [57]. Millis et al. [55] found that at 5 years post-injury (complicated mild to severe) cognitive functioning ranged from no measurable impairment to severe impairment. The course of cognitive recovery varies greatly among individuals. Millis et al. [55] found that 22.2 % of persons in the Traumatic Brain Injury Model Systems (TBIMS) national database demonstrated cognitive improvement during 1–5 years post-injury, while 62.6 % remained stable and 15.2 % deteriorated. The further decline of cognitive functioning during the recovery stage of TBI has also been reported by Till et al. [58]. Millis et al. [55] noted that the subgroup showing continued decline in cognitive functioning was the oldest group (e.g., middle age), with the next lower age group remaining stable, and the youngest group showing cognitive improvement. The declines were most evident on measures requiring cognitive flexibility and speeded performance and were of a great enough magnitude to be associated with functional declines. Bercaw et al. [59] suggested that possible reasons for this decline include medical comorbidities or emotional distress.

Cognitive performance measured during acute rehabilitation is useful in predicting 1-year outcomes, even above and beyond functional and injury severity factors. For example, neuropsychological status within the first month post-injury assessed during inpatient rehabilitation with a brief standard battery was predictive of handicap, functional outcomes, need for supervision, and employability at 1 year post-injury. An estimate of premorbid cognitive functioning (WTAR) was most predictive of outcomes at 1 year post-injury individually. A measure of executive functioning (TMT-B) also showed unique predictive power of functional independence (FIM) and general outcomes (GOS-E) [60].

TBI has been associated with increased risk of psychological disorders, both organically and situationally, with regard to reactions to injury and disability. This section primarily focuses on organically based changes which may occur following moderate to severe TBI, with some highlights of other causes and rates of disorders. Possible biological causes for psychological changes following TBI include the possibility that hypoxia leads to the release of free radicals and excitotoxic neurotransmitters. Additionally, neurochemical changes can occur subsequent to TBI, including effects on norepinephrine, serotonin, dopamine, and acetylcholine [84]. Anxiety and depression have been shown to have the strongest association with TBI and are perhaps the most commonly studied psychological changes. A meta-analysis by van Reekum et al. [85] revealed that the highest relative risks (RR) following TBI were for major depression (RR 7.5), bipolar disorder (RR 5.3), anxiety disorders (RR 2.0), and panic disorder (RR 5.8). Interestingly, although there are many pharmacologic approaches to dealing with these disorders in the medical and psychiatric literature, there are no approved medications for treating these disorders in those with TBI and medications are used off-label. For a review see Waldron-Perrine, Hanks, and Perrine [86].